Targeting Topics 13q2

Direct Retino-Raphe Projection Alters Serotonergic Tone and Affective Behavior.

Ren C, Luan L, Wui-Man Lau B, Huang X, Yang J, Zhou Y, Wu X, Gao J, Pickard GE, So KF, Pu M.

Neuropsychopharmacology Epub 2013.

Although recent work has shown that some intrinsically photosensitive retinal ganglion cells (ipRGCs) are responsible for processing nonimage-forming visual functions, it is unclear whether the ipRGCs or conventional RGCs modulate affective behavior. The authors injected 2 μg of melanopsin-SAP (Cat. #IT-44) into each eye of gerbils, or biotinylated CTB monoclonal antibody coupled to Streptavidin-ZAP (Cat. #IT-27). The data suggest that retino-raphe signals modulate dorsal raphe nucleus serotonergic tone and affective behavior.

Stable Respiratory Activity Requires Both P/Q-Type and N-Type Voltage-Gated Calcium Channels.

Koch H, Zanella S, Elsen GE, Smith L, Doi A, Garcia AJr, Wei AD, Xun R, Kirsch S, Gomez CM, Hevner RF, Ramirez JM.

J Neurosci 33(8):3633-3645, 2013.

Pharmacological experiments have suggested that sighs and normal respiration are highly dependent on calcium currents carried by P/Q channels. Using transgenic mice missing the Cav2.1 pore-forming α1A subunit the authors demonstrate that loss of P/Q-type calcium channels results in compromised breathing, sighing, neuromodulation, and leads to early death. A neurokinin-1 receptor antibody (Cat. #AB-N33AP) at a 1:500 dilution was used for immunohistochemistry in this work.

Single domain antibodies for the detection of ricin using silicon photonic microring resonator arrays.

Shia WW, Bailey RC.

Anal Chem 85(2):805-810, 2013.

A major hurdle to clear in the fight against bioterrorism is the ability to identify various biowarfare agents. One of the more difficult substances to identify is ricin. This work describes the use of single domain antibodies to identify ricin in a microring resonator array assay. Saporin (Cat. #PR-01) along with affinity purified chicken anti-saporin (Cat. #AB-17AP) were used as controls when constructing the assay. The results demonstrate the feasibility of using microring resonator arrays for the detection of biowarfare agents.

Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl(-) homeostasis.

Ferrini F, Trang T, Mattioli TA, Laffray S, Del’Guidice T, Lorenzo LE, Castonguay A, Doyon N, Zhang W, Godin AG, Mohr D, Beggs S, Vandal K, Beaulieu JM, Cahill CM, Salter MW, De Koninck Y.

Nat Neurosci 16(2):183-192, 2013.

Although morphine is the drug of choice in dealing with chronic pain, it paradoxically can produce a hyperalgesic state. The authors examined the issue from several different angles. One method was to eliminate spinal microglia of rats through the intrathecal application of 16-32 μg of Mac-1-SAP (Cat. #IT-33). 20 μg of saporin (Cat. #PR-01) was used as a control. It was found that P2X4 receptors expressed by microglia were necessary for the development of morphine hyperalgesia, but not morphine tolerance.

Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent measures of brain connectivity without overt memory deficits.

Brayda-Bruno L, Mons N, Yee BK, Micheau J, Abrous DN, Nogues X, Marighetto A.

Neurobiol Dis 54:372-381, 2013.

The authors examined whether partial degeneration of septo-hippocampal neurons alters brain activity patterns even without overt memory loss. Mice received 45 ng of mu p75-SAP (Cat. #IT-16) into the medial septal area. Lesioned animals had significantly altered functional activities in the brain, despite lack of an overt behavioral deficit. Some changes observed are also altered with the initial signs of Alzheimer’s disease.

Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

Hamlin AS, Windels F, Boskovic Z, Sah P, Coulson EJ.

PLoS One 8(1):e53472, 2013.

Alzheimer’s disease patients perform poorly on spatial navigation tests requiring either distal cues (allothetic) or body-centered cues (idiothetic). The authors used 0.2 μg bilateral infusions of mu p75-SAP (Cat. #IT-16) into the lateral ventricles of mice to examine the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals were similar to controls in contextual fear conditioning, spatial working memory, as well as several other parameters. But exploratory behavior requiring idiothetic signals was very disorganized, indicating that cholinergic cells are vital to idiothetic navigation.

Rapid beta-Amyloid Deposition and Cognitive Impairment After Cholinergic Denervation in APP/PS1 Mice.

Ramos-Rodriguez JJ, Pacheco-Herrero M, Thyssen D, Murillo-Carretero MI, Berrocoso E, Spires-Jones TL, Bacskai BJ, Garcia-Alloza M.

J Neuropathol Exp Neurol 72(4):272-285, 2013.

The authors investigated whether specific cholinergic neurodegeneration is responsible for the deposition of plaques. APPswe/PS1dE9 transgenic mice received bilateral icv injections of 1-1.2 μg of mu p75-SAP (Cat. #IT-16) into the basal forebrain. Although the transgenic mice show plaque deposition, they do not exhibit other signs of Alzheimer’s disease. Lesioned transgenic animals, however, displayed increased β-amyloid plaque deposition, increased Tau phosphorylation, and early memory impairment that worsened with age.

Targeted Delivery of Immunotoxin by Antibody to Ganglioside GD3: A Novel Drug Delivery Route for Tumor Cells.

Torres Demichelis V, Vilcaes AA, Iglesias-Bartolome R, Ruggiero FM, Daniotti JL.

PLoS One 8(1):e55304, 2013.

The authors used the mouse monoclonal antibody R24 against ganglioside G3 with Mab-ZAP (Cat. #IT-04) to test the viability of ganglioside G3 as a cancer therapy target. Varying concentrations of R24 were used on various cell lines with either 0.95 nM or 9.5 nM Mab-ZAP depending on the cell line. (See cover article for more information.)

Yohimbine anxiogenesis in the elevated plus maze requires hindbrain noradrenergic neurons that target the anterior ventrolateral bed nucleus of the stria terminalis.

Zheng H, Rinaman L.

Eur J Neurosci 37(8):1340-1349, 2013.

The anterior ventrolateral bed nucleus of the stria terminalis (vIBST) appears to be important for increased noradrenergic signaling to trigger anxiety-like behavior. 42.8 ng of anti-DBH-SAP (Cat. #IT-03) was administered to the vIBST of rats in bilateral injections. Elimination of noradrenergic neurons in the vIBST abolished yohimbine-induced anxiogenesis in an elevated plus maze, indicating that hindbrain noradrenergic neurons targeting the vIBST are involved in this mechanism.

Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: A model for Alzheimer’s disease.

Szigeti C, Bencsik N, Simonka AJ, Legradi A, Kasa P, Gulya K.

Brain Res Bull 94C:9-16, 2013.

192-IgG-SAP (Cat. #IT-01) has been used extensively to generate models of Alzheimer’s disease in rats. In this work, the authors detailed the time course of neuronal loss with an eye on potential recovery from the lesion. The nucleus basalis magnocellularis of rats was injected with 75 ng of 192-IgG-SAP (Cat. #IT-01) and long-term changes were tracked by immunohistochemistry. While some acetylcholinesterase neurons, considered cholinoceptive, were lost, choline acetyltransferase (cholinergic) neurons sustained a massive irreversible reduction in number.

Reduction in cholinergic interneuron density in the nucleus accumbens attenuates local extracellular dopamine release in response to stress or amphetamine.

Laplante F, Dufresne MM, Ouboudinar J, Ochoa-Sanchez R, Sullivan RM.

Synapse 67(1):21-29, 2013.

The authors examined whether excessive dopamine neurotransmission in the mesolimbic system is due to higher levels of presynaptic or postsynaptic dopamine. Rats received 250-ng bilateral injections of anti-ChAT-SAP (Cat. #IT-42) into the nucleus accumbens. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The data suggest that reduction of cholinergic interneurons in the nucleus accumbens suppresses presynaptic dopamine release. (Also see cover article for Q1 2013.)

Collateral damage and compensatory changes after injection of a toxin targeting neurons with the neurokinin-1 receptor in the nucleus tractus solitarii of rat.

Lin LH, Nitschke Dragon D, Talman WT.

J Chem Neuroanat 43(2):141-148, 2012.

Loss of substance P receptor (SPR)-expressing neurons in the nucleus tractus solitarii (NTS) results in reduced baroreflex strength and unstable arterial pressure. The neuronal population expressing the SPR also expresses several other types of receptors – such as N-methyl-D-aspartate (NMDA), and aalpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic (AMPA) receptors. The authors administered 9 ng of SSP-SAP (Cat. #IT-11) into the NTS and looked for differences in the expression of NMDA and AMPA receptors, as well as several different transporters and neuronal markers. he data suggest that the pathological effects of SSP-SAP lesions result from disruption of other neurotransmission systems than those using the SPR.

Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin’s lymphoma.

Kato J, O’Donnell RT, Abuhay M, Tuscano JM.

Oncoimmunology 1(9):1469-1475, 2012.

CD22 is a B-cell-specific antigen found on many B-cell malignancies. It is not expressed by stem cell precursors, and is rapidly internalized when bound by an antibody. In this work, the authors use a custom conjugate of anti-CD22 (mAb HB22.7) and saporin in a cytotoxicity assay on non-Hodgkin’s lymphoma cell lines, as well as in a mouse tumor model. The dosing for the tumor model was 1 mg conjugate per kg of animal. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The results indicate that CD22 is a potential therapeutic target for cancer therapy.

Sudden death following selective neuronal lesions in the rat nucleus tractus solitarii.

Talman WT, Lin LH.

Auton Neurosci 175(1-2):9-16, 2013.

The nucleus tracts solitarii (NTS) is the terminus of cardiovascular reflex nerves. Early work in this area sought to identify transmitters involved in the control of this region. The authors used SSP-SAP (Cat. #IT-11) and anti-DBH-SAP (Cat. #IT-03) to examine the role of NK-1r-expressing neurons and catecholaminergic neurons in baroreflex control in the NTS. Either 3 ng of SSP-SAP or 42 ng of anti-DBH-SAP was injected into the NTS of rats and baroreflex function was compared 7 days later. Although each toxin had a specific effect in terms of the types of cells eliminated, both toxins initiated a disturbance of the central baroreflex control that led to the death of some animals.

Intraneural OX7-saporin for neuroma-in-continuity in a rat model.

Mavrogenis AF, Pavlakis K, Stamatoukou A, Papagelopoulos PJ, Theoharis S, Zetahang Z, Soucacos PN, Zoubos AB.

Eur J Orthop Surg Traumatol 23(3):263-272, 2013.

The authors created a model of neuroma-in-continuity to explore the effect of OX7-SAP (Cat. #IT-02) on the neuroma. The left common peroneal, tibial or sciatic nerves were crushed, then at three and six weeks, the nerve cut distal to the site of nerve crush. Pressure microinjection of 2 μl of natural saline or 2 μl of the OX7-SAP was done at the nerve stump 2 days later. Sacrifice was done after 3 weeks. In all control specimens a neuroma-in-continuity was observed. In 19 of the 24 OX7-SAP specimens, histology showed inhibition of neuroma-in-continuity formation.

Physiology of the orexinergic/hypocretinergic system: a revisit in 2012.

Kukkonen JP.

Am J Physiol Cell Physiol 304(1):C2-32, 2013.

This review updates an original review from a decade ago on the subject of orexins. These neuropeptides have been shown to be involved in sleep, wakefulness, appetite, metabolism, stress response, reward/addiction, and analgesia. This broad spectrum of action affects many processes including neuronal excitation, synaptic plasticity, and cell death. he use of orexin-SAP (Cat. #IT-20, discontinued) in some of this work is discussed.